Special Feature: The Neandertal Genome

Human-Neandertal Comparisons

Comparisons of the human genome to the genomes of Neandertals and apes can help identify features that set modern humans apart from other hominin species. In particular, the Neandertal genome sequence can now be used to catalog changes that have become "fixed" (are invariant within a population or species) in modern humans during the last few hundred thousand years and should be helpful for identifying genes affected by positive selection since humans diverged from Neandertals.

To help make informative comparisons, Green et al. sequenced the genomes of 5 present-day individuals from different parts of the world: southern Africa, West Africa, Papua New Guinea, China, and western Europe (see map). They then compared the genomes of these individuals with the genomes of the Neandertal and the chimpanzee, and looked both for specific regions shared by present-day humans but lacking in Neandertals and regions showing high frequencies of more recently evolved (derived) sequences. These regions signal the presence of mutations that occurred and swept to either high frequency or fixation after humans and Neandertal diverged, and that may have contributed to modern human-specific traits.

Using this comparative approach, Green et al. came up with a list of 20 candidate regions that may have been affected by positive selection in ancestral modern humans. Five of these regions contain no protein-coding genes and may thus include structural or regulatory elements. Among the remaining 15 regions, the team identified genes involved in metabolism and cognitive and cranial development, which suggests that aspects of these processes may have been functionally important for the evolution of modern humans.

For more on Neandertal-modern human comparisons see the News story by A. Gibbons.

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Five modern human genomes. Locations of present-day individuals whose genomes were sequenced by Green et al. for comparative analyses.

Evidence of Admixture

Substantial controversy surrounds the question of whether Neandertals interbred with modern humans. To address this question, Green et al. tested whether Neandertals are more closely related to some present-day humans than to others.* Because modern humans are believed to have originated in Africa, if Neandertals diverged from modern humans before present-day populations began to differentiate, one would expect Neandertal sequences to match sequences from non-Africans and Africans to the same extent. Unexpectedly, the researchers found that Neandertals share more genetic variants with present-day non-Africans than with Africans. These results can be explained if gene flow occurred from Neandertals into the ancestors of non-Africans.

The observation that the Neandertal genome appears as closely related to the genome of a Chinese and a Papua New Guinean individual as to the genome of a French individual is particularly surprising as there is, to date, no fossil evidence that Neandertals existed in East Asia or Papua New Guinea. Green et al. thus suggest that gene flow between Neandertals and modern humans occurred prior to the divergence of European and Asian populations. Based on comparative genomic data, as well as a mathematical model of gene flow, the authors further estimate that between 1 and 4% of the genomes of people in Eurasia may be derived from Neandertals.

*For a description of additional methods used by Green et al. to detect gene flow between Neandertals and modern humans, see the News story by A. Gibbons.

Implications for Modern Human Origins

There are two major competing hypotheses about the origins of modern humans. The "Out of Africa" hypothesis posits that modern humans evolved from a small population in Africa and replaced all other hominin populations, including Neandertals, as they migrated into Europe and Asia. The simplest form of this model assumes no interbreeding between modern and ancestral human populations. In contrast, the "Multiregional" hypothesis holds that modern humans evolved in several regions of the world simultaneously. According to this view, archaic humans were not replaced by anatomically modern humans, but rather, gene flow between Africa, Europe, and Asia, led to the evolution of modern humans from local populations.

The finding that Neandertals are on average closer to individuals in Eurasia than to individuals in Africa thus presents a challenge to the strictest version of the "Out of Africa" model; however variations of this model are plausible. Green et al. suggest that mixing of early modern humans ancestral to present-day non-Africans with Neandertals is likely to have occurred in the Middle East prior to their expansion into Eurasia. The authors contend that this scenario is compatible with the archaeological record, which shows that modern humans appeared in the Middle East before 100,000 years ago while the Neandertals existed in the same region after this time, perhaps until 50,000 years ago.

Although the Green et al. analyses are suggestive of admixture, the role of Neandertals in the genetic ancestry of humans outside of Africa was likely relatively minor given that only a few percent of the genomes of present-day people outside of Africa appear to be derived from Neandertals. More fossil and genetic data will help researchers further resolve the relationships between our early ancestors and how they shaped modern human evolution.